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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-7-8
pubmed:abstractText
Despite extensive work in the field of glioblastoma research no significant increase in survival rates for this devastating disease has been achieved. It is known that disturbance of intracellular Ca(2+) ([Ca(2+)](i)) and intracellular pH (pH(i)) regulation could be involved in tumor formation. The sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) is a major regulator of [Ca(2+)](i). We have investigated the effect of inhibition of SERCA by thapsigargin (TG) on [Ca(2+)](i) and pH(i) in human primary glioblastoma multiforme (GBM) cells and GBM cell lines, compared with normal human astrocytes, using the fluorescent indicators fura-2 and BCECF, respectively. Basal [Ca(2+)](i) was higher in SK-MG-1 and U87 MG but not in human primary GBM cells compared with normal astrocytes. However, in tumor cells, TG evoked a much larger and faster [Ca(2+)](i) increase than in normal astrocytes. This increase was prevented in nominally Ca(2+)-free buffer and by 2-APB, an inhibitor of store-operated Ca(2+) channels. In addition, TG-activated Ca(2+) influx, which was sensitive to 2-APB, was higher in all tumor cell lines and primary GBM cells compared with normal astrocytes. The pH(i) was also elevated in tumor cells compared with normal astrocytes. TG caused acidification of both normal and all GBM cells, but in the tumor cells, this acidification was followed by an amiloride- and 5-(N,N-hexamethylene)-amiloride-sensitive recovery, indicating involvement of a Na(+)/H(+) exchanger. In summary, inhibition of SERCA function revealed a significant divergence in intracellular Ca(2+) homeostasis and pH regulation in tumor cells compared with normal human astrocytes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
289
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C361-71
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Changes in intracellular Ca2+ and pH in response to thapsigargin in human glioblastoma cells and normal astrocytes.
pubmed:affiliation
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural